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Recent evidence indicate that melanotan II (MTII) reduces body mass independently of caloric reduction. Because MTII induces a transient hypophagia, caloric reduction is still considered a primary mechanism for MTII-mediated body mass loss. To examine the contribution of caloric reduction to long-term body mass loss in response to MTII, we centrally infused MTII or vehicle in ad libitum fed (MTII and Control) animals in comparison with a group of animals that were pair-fed (PF) to the MTII group. Food intake and body mass were recorded daily, and body composition was assessed biweekly. The present study demonstrates that central MTII-mediated body mass loss is only partially mediated by caloric restriction, and the long-term body mass loss is independent of the initial hypophagia. More importantly, central MTII administration induced a rapid but sustained fat mass loss, independently of caloric reduction. MTII-treated animals preserved their lean/fat mass ratio throughout the study, whereas PF animals underwent a transient reduction of lean/fat mass ratio that was only normalized when food intake returned to Control level. In summary, it can be concluded that activation of the central melanocortin system in rats persistently reduces body and fat mass independently of caloric reduction. Key words: melanotan II, body mass, body fat, lean/fat mass ratio, caloric reduction. Des donnees recentes montrent que melanotan II (MTII) entraine une diminution de la masse corporelle independamment de la diminution des calories. Comme MTII engendre une hypophagie transitoire, la diminution des calories est toujours consideree comme etant un mode d'action principal de la perte de masse corporelle mediee par MTII. En vue d'examiner la contribution de la diminution des calories a la perte de masse corporelle a long terme en reaction a MTII, nous avons perfuse MTII ou un vehicule centralement chez des animaux nourris ad libitum (MTII et temoin) comparativement a un groupe d'animaux nourris de maniere appariee (NA) avec le groupe MTII. Nous avons consigne quotidiennement l'apport alimentaire et la masse corporelle ainsi qu'evalue la composition corporelle une semaine sur deux. La presente etude montre que la perte de masse corporelle mediee par l'administration centrale de MTII n'est que partiellement mediee par la restriction des calories, et que la perte de masse corporelle a long terme est independante de l'hypophagie initiale. De maniere encore plus importante, l'administration centrale de MTII engendrait une perte de masse adipeuse rapide, mais soutenue, independamment de la diminution des calories. Les animaux exposes a MTII conservaient leur ratio de masse maigre/masse adipeuse tout au long de l'etude, alors que les animaux NA ont subi une diminution transitoire du ratio masse maigre/masse adipeuse qui revenait a la normale uniquement quand l'apport alimentaire revenait au niveau des animaux temoins. En resume, on peut conclure que l'activation du systeme central de la melanocortine chez le rat entraine une diminution persistante de la masse corporelle et adipeuse, independamment de la diminution des calories. [Traduit par la Redaction] Mots-cles : melanotan II, masse corporelle, masse corporelle adipeuse, ratio masse maigre/masse adipeuse, diminution des calories., Isabelle^Green, Sara M.^Morgan, Drake^Carter, Christy S.^Tumer, Introduction The central melanocortin system modulates energy homeostasis predominantly through the pro-opiomelanocortin cleavage product, a-melanocyte-stimulating hormone (a-MSH), which suppresses food intake and energy storage [...]

Abstract Background Many studies of cocaine-responsive gene expression have focused on changes occurring during cocaine exposure, but few studies have examined the persistence of these changes with cocaine abstinence. Persistent changes in gene expression, as well as alterations induced during abstinence may underlie long-lasting drug craving and relapse liability. Results Whole-genome expression analysis was conducted on a rat cocaine binge-abstinence model that has previously been demonstrated to engender increased drug seeking and taking with abstinence. Gene expression changes in two mesolimbic terminal fields (mPFC and NAc) were identified in a comparison of cocaine-naïve rats with rats after 10 days of cocaine self-administration followed by 1, 10, or 100 days of enforced abstinence (n = 6-11 per group). A total of 1,461 genes in the mPFC and 414 genes in the NAc were altered between at least two time points (ANOVA, p < 0.05; ± 1.4 fold-change). These genes can be subdivided into: 1) changes with cocaine self-administration that do not persist into periods of abstinence, 2) changes with cocaine self-administration that persist with abstinence, 3) and those not changed with cocaine self-administration, but changed during enforced abstinence. qPCR analysis was conducted to confirm gene expression changes observed in the microarray analysis. Conclusions Together, these changes help to illuminate processes and networks involved in abstinence-induced behaviors, including synaptic plasticity, MAPK signaling, and TNF signaling.

Ref.: Can. J. Physiol. Pharmacol. 96(3): 308-312 (2018) dx.doi.org/10.1139/cjpp-2017-0440. The Acknowledgements section should have specified 'This work was supported by a grant from the National Institutes of Health, USA (DK091710).' [...]

In recent years a number of beneficial health effects have been ascribed to the renin-angiotensin system (RAS) that extend beyond lowering blood pressure, primarily mediated via the angiotensin-converting enzyme-2 (ACE2)/angiotensin (1-7) or Ang(1-7)/MAS receptor axis. Moreover, once thought as merely a systemic effector, RAS components exist within tissues. The highest tissue concentrations of ACE2 mRNA are located in the gut making it an important target for altering RAS function. Indeed, genetically engineered recombinant probiotics are promising treatment strategies offering delivery of therapeutic proteins with precision. An Ang(1-7) secreting Lactobacillus paracasei (LP) or LP-A has been described for regulation of diabetes and hypertension; however, we are the first to the best of our knowledge to propose this paradigm as it relates to aging. In this Research Practice manuscript, we provide proof of concept for using this technology in a well-characterized rodent model of aging: the Fisher344 x Brown Norway Rat (F344BN). Our primary findings suggest that LP-A increases circulating levels of Ang(1-7) both acutely and chronically (after 8 or 28 treatment days) when administered 3× or 7×/week over 4 weeks. Our future preclinical studies will explore the impact of this treatment on gut and other age-sensitive distal tissues such as brain and muscle. [ABSTRACT FROM AUTHOR]